Rapid CommunicationRegulatory T cells (CD4+CD25brightFoxP3+) expansion in systemic sclerosis correlates with disease activity and severity
Introduction
Regulatory T (Treg) cells play a critical role in maintenance of immunologic self-tolerance as well as regulation of immune responses. Decreased numbers and/or defective suppressive function of Treg cells have been reported in patients with a variety of autoimmune and allergic disorders [1]. In systemic lupus erythematosus or rheumatoid arthritis, for example, Treg cell dysfunction is believed to contribute to mechanisms of initiation and/or maintenance of high disease activity [2], [3], [4].
Systemic sclerosis (SSc) represents one of the autoimmune disorders where the role and function of Treg cells may be of particular interest because of the tight involvement of tissue growth factor beta (TGF-β) in both the pathogenesis of SSc and immunobiology of Treg cells, as TGF-β is vital to their development, survival and activity [5], [6], [7].
Some studies have demonstrated increased, not decreased, percentages of CD4+CD25+ cells in peripheral blood of patients with SSc [8], [9]. One recent study confirmed the existence expanded pool of true CD4+CD25bright FoxP3+ Treg cells in patients with SSc [10]. However, the relationship of Treg cells numbers to the activity or severity of SSc have not been previously investigated, and the functional potential of these cells has not been fully evaluated.
The primary aim of this study was to evaluate the numbers of and production of cytokines by Treg cells in patients with SSc, with correlation to activity and/or severity of the disease.
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Patients
The study was approved by a local Helsinki Committee. Ten patients with SSc, diagnosed according to 1980 American Rheumatism Association criteria, gave informed consent and were enrolled in the study. A healthy volunteer (control) was matched to every patient by age and gender. Twenty milliliters of peripheral blood were drawn from a patient and a matched control for each single experiment.
Cells
PMBCs were isolated on Lyphoprep (Axis-Shield). CD4+ T cells were isolated by magnetic cell sorting with
Patients
Ten consecutive patients with systemic sclerosis, followed by the rheumatology unit of Bnai Zion Medical Center in Haifa, Israel, gave informed consent and were enrolled to this study in the time period from 12/2008 to 3/2009. All patients fully satisfied the 1980 American Rheumatism Association criteria for systemic sclerosis. The clinical and laboratory characteristics of the patients are shown in Table 1. The activity of SSc was calculated by Valentini Disease Activity Index, and the
Discussion
Treg cells represent up to 10% of the CD4+ T-cell subset in the peripheral blood, with responsibility for the regulation of autoreactive T-cells. Depletion of Treg cells leads to the development of multisystem autoimmune disease in animal models [14]. Decreased numbers or alterations in functional activity of Treg cells have been reported in association with several human chronic inflammatory and autoimmune diseases [2], [3], [4]. As such, the results of this study stand out in demonstrating
Acknowledgments
The authors thank Mrs. Katalin Halasz for her excellent technical assistance and Dr. Neve Tov for his advice on the statistical analysis.
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2020, Journal of Dermatological ScienceCitation Excerpt :In this study, we showed that effector Treg cells are increased in patients with BP. Similarly, Foxp3+ Treg cells were reported to positively correlate with disease severity in patients with psoriasis and systemic sclerosis [30,31]. Taking the above together, we speculate that effector Treg cells might suppress COL17-specific autoreactive T cells in steady state in some individuals, such as those who possess DQB1*03:01 [32], and that when COL17-specific T cells are activated by some trigger such as aging, drugs, burns, trauma, infections, neurological disorders or other unknown cause [33,34], effector Treg cells might expand to suppress those autoreactive T cells but not enough to prevent the development of BP.
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These authors contributed equally to the work.